Oligodendrocytes are a type of glial cell found in the central nervous system that are formed by maturation of oligodendrocyte-type 2 astrocyte (O-2A) progenitor cells (abbreviated as OPC in the present application), and are mainly responsible for the formation of myelin sheath. OPC are the products of further differentiation of glial progenitor cells that have differentiated from neural stem cells. Although OPC actively undergo repeated cell division during organogenesis, a portion of those cells mature soon after birth and begin to differentiate into oligodendrocytes, and in adults, differentiate into oligodendrocytes, with the exception of some cells (adult OPC). Adult OPC observed in adults differ from proliferating OPC observed during organogenesis and soon after birth in that they are in a dormant state without hardly any proliferation. However, adult OPC retain the ability to differentiate and differentiate into oligodendrocytes in the presence of a suitable stimulus. In other words, adult OPC are a type of somatic stem cells.
Proliferating OPC harvested from the optic nerve of rats soon after birth have been reported to not differentiate into oligodendrocytes if cultured in serum-free media containing platelet-derived growth factor (PDGF) in an environment having an oxygen concentration of 20% by volume, but differentiate into oligodendrocytes when cultured in serum-free media containing PDGF and thyroid hormone, and proliferating OPC have been reported to be able to be sub-cultured in serum-free media containing PDGF over a long period of time of one year or longer while retaining the properties of proliferating OPC but without undergoing replicative senescence (see, for example, Non-Patent Document 2). In addition, retinoic acid has been reported to induce differentiation of OPC into oligodendrocytes in the same manner as thyroid hormone, and both have been reported to function mediated by the same p53-dependent intracellular signaling pathway (see, for example, Non-Patent Document 3).